This randomized phase III trial studies how well eribulin mesylate or paclitaxel work as first- or second-line therapy in treating patients with stage IIIC-IV breast cancer that has come back. Drugs used in chemotherapy, such as eribulin mesylate and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
PRIMARY OBJECTIVES: I. To demonstrate that patient-reported Patient-Report Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) data will be able to detect differences in symptoms between participants treated witheribulin mesylate (eribulin) and standard weekly paclitaxel at 12 weeks. II. To validate rs7349683 in EPHA5 as a predictor of peripheral neuropathy from treatment with a microtubule targeting agent (i.e., eribulin or paclitaxel). SECONDARY OBJECTIVES: I. To compare overall survival, progression free survival (PFS), objective response rate (ORR), duration of response (DOR), and time to treatment failure (TTF) in patients receiving eribulin versus standard weekly paclitaxel. II. To compare the 12 month rate of disease progression in patients receiving eribulin versus standard weekly paclitaxel. III. To evaluate the clinical value and feasibility of collecting patient-reported symptom toxicity information via the Patient-Report Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). IV. To further validate the PRO-CTCAE sensory neuropathy items. V. To compare patient reported neurotoxicity between arms using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) instrument. VI. To assess the toxicities in patients receiving eribulin versus standard weekly paclitaxel. CORRELATIVE OBJECTIVES: I. To compare new metastasis free survival in patients receiving eribulin versus standard weekly paclitaxel. II. To explore the relationship between common single nucleotide polymorphisms in FGD4, FZD3, and VAC14 as predictors of peripheral neuropathy from treatment with a microtubule targeting agent (i.e., eribulin or paclitaxel). III. To evaluate circulating nucleosomes and the apoptosis associated M30 neo-epitope as potential biomarkers associated with clinical benefit from treatment with eribulin specifically or the microtubule dynamics inhibitors in general. VI. To evaluate tubulin isotype expression, mutations, and signaling pathway modifications in tumor tissue as potential biomarkers associated with clinical benefit from treatment with eribulin specifically or the microtubule dynamics inhibitors in general. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
201
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Illinois
Chicago, Illinois, United States
Cumulative Dose Level Triggering a Grade 2 or Higher Neuropathy Event.
To validate rs7349683 in EPHA5 as a predictor of peripheral neuropathy from treatment with a microtubule targeting agent (i.e., eribulin or paclitaxel) over the first 6 months of treatment we will compare the median cumulative dose level triggering a grade 2 or higher neuropathy event.
Time frame: 6 months
Mean Change in Patient Reported PRO-CTCAE
To demonstrate that patient-reported PRO-CTCAE data will be able to detect differences in symptoms between participants treated with eribulin and standard weekly paclitaxel at 12 weeks we will compare the mean change of overall Pro-CTCAE score by treatment arm. The overall Pro-CTCAE score is a normalized score scaled from 20 questions, each with a possible 1-5 patient selection, creating an overall score (0-100) where 0 represents the best outcome and 100 represents the worst possible outcome. The mean change from baseline to week 12 is reported.
Time frame: 12 weeks
Overall Survival (OS)
The primary analysis will use the stratified log-rank tests, as described for overall survival. As a secondary analysis we will use a multivariable Cox proportional hazard model to estimate adjusted hazard ratios for eribulin mesylate over standard weekly paclitaxel, study stratification factors, and covariates for known prognostic factors, including disease free interval and visceral versus non-visceral metastases. Survival functions will be summarized using the Kaplan-Meier method according to treatment group.
Time frame: 81 months
Objective Tumor Response Rate
Objective tumor response rate is assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: 64 months
Duration of Response
Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals. Duration of response is the time between a tumor response and progression.
Time frame: 75 months
Time to Treatment Failure
Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.
Time frame: 64 months
Incidence of Treatment Related Adverse Events
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT). Events determined to be possibly or probably attributed to a medical treatment suggest there is evidence to indicate a causal relationship between the drug and the adverse event. The number of patients that experienced an AE, of any grade, determined to be possibly or probably attributed to a medical treatment will be reported by arm.
Time frame: 64 months
Time to New Metastasis
Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.
Time frame: 81 months
Progression Free Survival Assessed by RECIST 1.1 Criteria
Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals. Progression free survival time is the time from date of randomization to the date of first progression or death.
Time frame: 80 months
Patients With Reported Neurotoxicity
Additional analyses will include the previously described analysis conducted over the first 24 weeks; a comparison of the incidence of patient-reported maximum score \>= 3 between arms through 12 and 24 weeks using chi-squared testing for each item; and a comparison of the time to patient-reported score \>= 3 between arms using Kaplan-Meier and log-rank analyses. Further, these three endpoints will be compared between patient- and clinician-report overall and within arms using appropriate paired analyses.
Time frame: 24 weeks
Validation of PRO-CTCAE Sensory Neuropathy Item
The PRO-CTCAE sensory neuropathy items will be further validated by computing Pearson correlations between each item, severity and interference, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20 )sensory scale score at baseline, 12 and 24 weeks.
Time frame: At baseline, 12, and 24 weeks
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University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Illinois CancerCare-Peoria
Peoria, Illinois, United States
Carle Cancer Center NCI Community Oncology Research Program
Urbana, Illinois, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, United States
Iowa-Wide Oncology Research Coalition NCORP
Des Moines, Iowa, United States
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